This study aimed to determine the antibiofilm activity of seawater microbes against Vibrio cholerae (VCO1) through functional metagenomics approach. A metagenomic library was constructed from Palk Bay seawater and the library was screened to identify the biofilm inhibitory metaclone. Metaclone SWMC166 (harbouring ∼30 kb metagenomic insert) was found to exhibit antibiofilm activity against VCO1. The biofilm inhibitory potential of partially purified ethyl acetate extract of SWMC166 (EA166) was further evaluated through microscopic studies and biochemical assays. Further, EA166 treated VCO1 divulged up-regulation of genes involved in high cell density-mediated quorum sensing (QS) pathway which was analysed by real-time PCR. In order to identify the genes of interest (within ∼30 kb insert), subcloning was performed through shotgun approach. Small molecules from positive subclones SC5 and SC8 were identified through HRLC-MS analysis. Resulted small molecules were docked against QS receptors of V. cholerae to identify the bioactive metabolites. Docking studies revealed that totally seven metabolites were able to interact with QS receptors that can possibly trigger the QS cascade and sequentially inhibit the biofilm formation and virulence factors of VCO1.
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http://dx.doi.org/10.1016/j.mcp.2018.03.003 | DOI Listing |
Cell Commun Signal
January 2025
Department of Anesthesiology, The Affiliated Hospital of Southwest Medical University, No. 25, Taiping Road, Lu Zhou, Luzhou, Sichuan, 646000, China.
This review comprehensively explores the critical role of calcium as an essential small-molecule biomessenger in skeletal muscle function. Calcium is vital for both regulating muscle excitation-contraction coupling and for the development, maintenance, and regeneration of muscle cells. The orchestrated release of calcium from the endoplasmic reticulum (ER) is mediated by receptors such as the ryanodine receptor (RYR) and inositol 1,4,5-trisphosphate receptor (IP3R), which is crucial for skeletal muscle contraction.
View Article and Find Full Text PDFCell Mol Biol Lett
January 2025
Enzymology and Metabolism Group, Luxembourg Centre for Systems Biomedicine, University of Luxembourg, L-4367, Belvaux, Luxembourg.
Background: Metabolism is error prone. For instance, the reduced forms of the central metabolic cofactors nicotinamide adenine dinucleotide (NADH) and nicotinamide adenine dinucleotide phosphate (NADPH), can be converted into redox-inactive products, NADHX and NADPHX, through enzymatically catalyzed or spontaneous hydration. The metabolite repair enzymes NAXD and NAXE convert these damaged compounds back to the functional NAD(P)H cofactors.
View Article and Find Full Text PDFSci Rep
January 2025
Department of Breast Surgery, Cancer Hospital of Shantou University Medical College, No. 7 Raoping Road, Shantou, 515041, Guangdong, China.
Uterine Corpus Endometrial Carcinoma (UCEC) represents a common malignant neoplasm in women, with its prognosis being intricately associated with available therapeutic interventions. In the past few decades, there has been a burgeoning interest in the role of mitochondria within the context of UCEC. Nevertheless, the development and application of prognostic models predicated on mitochondrial-related genes (MRGs) in UCEC remains in the exploratory stages.
View Article and Find Full Text PDFCommun Biol
January 2025
Obsidian Therapeutics, Cambridge, MA, USA.
Adoptive cell therapies (ACT) have shown reduced efficacy against solid tumor malignancies compared to hematologic malignancies, partly due to the immunosuppressive nature of the tumor microenvironment (TME). ACT efficacy may be enhanced with pleiotropic cytokines that remodel the TME; however, their expression needs to be tightly controlled to avoid systemic toxicities. Here we show T cells can be armored with membrane-bound cytokines with surface expression regulated using drug-responsive domains (DRDs) developed from the 260-amino acid protein human carbonic anhydrase 2 (CA2).
View Article and Find Full Text PDFNat Commun
January 2025
Zhejiang Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang Key Laboratory of Frontier Medical Research on Cancer Metabolism, Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China.
Liver fibrosis is a critical liver disease that can progress to more severe manifestations, such as cirrhosis, yet no effective targeted therapies are available. Here, we identify that ATF4, a master transcription factor in ER stress response, promotes liver fibrosis by facilitating a stress response-independent epigenetic program in hepatic stellate cells (HSCs). Unlike its canonical role in regulating UPR genes during ER stress, ATF4 activates epithelial-mesenchymal transition (EMT) gene transcription under fibrogenic conditions.
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